Unlike almost all the cervical, penile, vulvar, and anal cancers, where Human papilloma virus has long known to play a vital role, a causative link between carcinogenic Human papilloma virus and lung cancer have been found to be highly variable and contradictory. Data also shows geography and race-dependenty. Apart from etiological factors, viral carcinogen can manipulate the cell cycle, hamper cell apoptosis and also interrupt the cell division in host cell which lead to the lung cancer. Molecular studies of carcinogenic Human papilloma virus have found that E6/E7 acts as mitotic mutators which play an important role in pathogenicity and oncogenicity. Analysis of genome sequence of Human papilloma virus revealed that ORF having conserved in early region, E6 and E7 required for viral pathogenicity and oncogenicity can be the suitable target for RNAi technology. RNAi works by silencing or turning off gene expression to control pathogenicity and oncogenicity by blocking its replication processes. Therefore, the work is done on the basis of rational siRNA designing method by targeting viral oncogenic E6 and E7 genes of Human papilloma virus types16 & 18. Searching siRNA target sequences, multiple sequence alignment, forecasting secondary structure and RNA-RNA interaction prediction was done by various computational software tools for designing RNA-based therapeutics (siRNA). In this study, four effective siRNA were predicted rationally for oncogenic E6 and E7 genes of Human papilloma virus types 16 & 18 which might be used as a potential RNA based therapeutics to control the rate of carcinogenesis and degree of oncogenicity. The outcome of this study provides a basis of the researchers towards understating to development of RNA-based therapeutics (siRNA) at genomic level.